肌肉微环境与恶液质的发生、 发展

恶液质是肿瘤患者最为常见的合并症之一。其中骨骼肌丢失是恶液质的核心表现,特别是肌肉蛋白大量降解导 致骨骼肌萎缩是其重要的病理生理改变。肿瘤状态下,不但其骨骼肌的代谢异于正常代谢,导致能量消耗的增加和无效的 能量利用,导致恶液质发生,而且肌肉微环境的变化与恶液质的发生、发展密切相关,其中由于众多生物因子直接或间接 的作用,均可导致肌肉蛋白分解,骨骼肌萎缩,促使恶液质发生、发展。恶液质是肿瘤患者死亡的主要原因之一,它不仅 出现在近一半的恶性肿瘤患者中,而且还占据了恶性肿瘤患者死亡原因的20%~40%,并随进程发展而加重。由于恶液质状 态下的骨骼肌萎缩与应激、饥饿等情况引起的骨骼肌萎缩机制大相径庭,且后果比较严重,目前干预手段不可逆转其进程, 所以定期精确测量患者人体体成分就显得尤为重要,动态观察骨骼肌变化,尽早发现,及时干预。     

左旋肉碱经Runx2/COL1A1通路抑制老年鼠肿瘤恶 液质的骨骼肌纤维化

目的 探讨左旋肉碱经Runx2/COL1A1通路抑制老年鼠肿瘤恶液质的骨骼肌纤维化。方法 用结肠癌MC38细胞在C57老 年鼠右侧腹股沟皮下植瘤构建肿瘤恶液质模型，实验分为非荷瘤组、荷瘤组和左旋肉碱组，并进行相应干预。实验结束后取一侧腓 肠肌称重，行苏木精⁃伊红染色（HE染色）和Masson染色后，分别测量腓肠肌横截面积和胶原纤维面积占比；对侧腓肠肌提取总蛋白， 蛋白质印迹法检测Runx2和COL1A1蛋白水平。体外实验用转化生长因子-β1（TGF-β1）诱导NIH/3T3细胞，建立体外纤维化模型， 经左旋肉碱干预后，分别提取总蛋白和mRNA，蛋白质印迹法检测Runx2和COL1A1蛋白水平，并用qRT⁃PCR检测COL1A1 mRNA水 平，转染cDNA⁃Runx2验证左旋肉碱通过Runx2调控COL1A1。结果 三组进行比较，荷瘤组腓肠肌重量明显低于非荷瘤组（[ 98.12± 17.04）mg 比 (122.18±6.91）mg（] P<0.05）；荷瘤组腓肠肌横截面积（207.46±54.55）µm2 显著低于非荷瘤组（488.61±46.72）µm2 和左旋肉 碱组（434.54±113.84）µm（2 P<0.05）；胶原纤维面积占比荷瘤组（9.69±1.55）%明显高于左旋肉碱组（5.48±1.19）%和非荷瘤组（3.88±0.86）% （P<0.05）。蛋白质印迹法结果显示，与其他两组相比，荷瘤组Runx2和COL1A1高表达（P<0.05）。体外研究表明，左旋肉碱可逆转 TGF⁃β1诱导的Runx2蛋白和COL1A1 mRNA高表达。过表达Runx2结果证实左旋肉碱通过抑制Runx2蛋白的表达下调COL1A1 mRNA。 结论 左旋肉碱通过降低Runx2/COL1A1改善老年鼠肿瘤恶液质的骨骼肌纤维化。     

肿瘤恶液质的诊治

肿瘤恶液质是以肿瘤患者骨骼、内脏的肌肉消耗为特征,伴或不伴有食欲减退、厌食、饱胀感、体重下降、肌肉萎缩、乏力、贫血、水肿、低蛋白血症等一系列临床并发症。肿瘤恶液质的存在使患者的抗肿瘤治疗难以进行,影响患者生存;同时临床并发症的出现也严重影响了患者的生活质量。临床中,肿瘤患者恶液质的发病率高,死亡率高,而且一旦进入恶液质期难以逆转。因此早期发现、早期干预才能改善体重、防止肌肉丢失、减轻恶液质的相关症状,以达到提高生活质量、延长生存、改善预后的治疗目的。本文以肿瘤恶液质的定义为基础,从三大营养物质的代谢改变出发,总结了目前关于肿瘤恶液质可能的发病机制,进而阐述了肿瘤恶液质的筛查与评定及诊断要点,综述了对应的治疗策略及方法,包括营养干预、运动干预、心理干预及其他药物干预等,并对未来肿瘤恶液质多学科规范化诊疗进行了展望,期望通过多学科诊疗（MDT）的模式,能为肿瘤恶液质患者的早诊早治、延长生存、改善预后提供新的理念,创建新的平台。     

肿瘤恶液质临床诊断与治疗指南（2020版）

恶液质（cachexia）是一个全球范围的严重疾病，发病率逐年递增，常伴发于多种慢性疾病。其中，肿瘤恶液质（cancer cachexia）发病率最高，是各种晚期恶性肿瘤的常见并发症，进展期恶性肿瘤约60%~80%可出现恶液质，约20%肿瘤患者死于恶液质。因此，肿瘤恶液质的准确临床诊断和制定有效干预措施对于晚期恶性肿瘤患者的长期生存具有重要意义。基于此，中国抗癌协会肿瘤营养专业委员会依据肿瘤恶液质筛查、诊断、评估、治疗等方面研究证据和临床经验进行分析、讨论和总结，制订了《肿瘤恶液质临床诊断与治疗指南（2020版）》，以供临床医师参考。      

肾癌细胞系SN12C 和786-O 无血清培养的干细胞球特性的比较*

目的:本研究通过比较SN12C 和786-O两株肾癌细胞系中肿瘤干细胞特征的差异性,初步探讨筛选肾癌干细胞更有效的方法。方法:以无血清培养法培养SN12C 和786-O细胞,比较其在不同时间形成肿瘤干细胞球的差异;应用流式细胞术分析SN12C 和786-O球体细胞中干细胞标志物的表达情况;利用裸鼠体内成瘤模型检测SN12C 和786-O球体细胞成瘤能力。结果:SN12C 较786-O更易形成肿瘤干细胞球且所需时间更短,即786-O在无血清培养的第7 天开始形成规则的球体,而SN12C 则在第5 天就已形成规则的球体。SN12C 和786-O球体细胞中干细胞指标表达量亦有显著性差异,在SN12C 球体细胞中CD133、CD44、Nanog和Oct3/ 4 比例明显高于786-O球体细胞,差异具有统计学意义（P < 0.05）。 裸鼠体内的成瘤能力实验发现SN12C 明显强于786-O球体细胞。结论:SN12C 肾癌细胞系通过无血清培养方法富集肿瘤干细胞球明显多于786-O,是获得肿瘤干细胞较好的研究对象。      

香烟烟雾激活肺癌细胞Wnt/β-catenin信号途径的机制研究

背景与目的：香烟烟雾诱导的炎性反应可显著促进肺肿瘤的生长,本研究通过体内外实验明确香烟烟雾激活肺癌细胞Wnt/β-catenin信号途径的机制。方法：利用尾静脉注射鼠Lewis肺癌细胞方法建立小鼠肺癌模型,然后采用香烟烟雾对其进行刺激,诱发炎性反应。免疫组化方法检测小鼠和人肺肿瘤组织中CD68、肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)和无磷酸化β-catenin的表达。采用Transwell^®插入式细胞培养皿共培养人巨噬细胞和人肺癌细胞株A549细胞。采用蛋白质印迹法(Western blot)检测A549细胞中无磷酸化β-catenin的表达及磷酸化的GSK-3β和Akt蛋白的表达。结果：免疫组化结果显示,香烟烟雾刺激肺肿瘤负荷小鼠后,其肿瘤组织中巨噬细胞CD68⁺、TNF-α和无磷酸化β-catenin的表达均明显高于对照组。肺癌患者肿瘤组织中,CD68和TNF-α的阳性表达均明显高于正常组织。肺腺癌和鳞癌的无磷酸化β-catenin的染色阳性率分别为68.9%和62.2%,其阳性率与患者吸烟与否及肿瘤分期有关,差异有统计学意义(P均＜0.05),并且CD68⁺的细胞数在无磷酸化β-catenin染色阳性的标本中显著升高(P＜0.01)。Western blot检测结果显示,不同浓度香烟抽提物(cigarette smoke extract,CSE)刺激共培养细胞后,A549细胞中无磷酸化β-catenin的表达随着CSE浓度的增加而显著上升。在加入TNF-α中和抗体后,A549细胞中无磷酸化β-catenin的表达被抑制。用TNF-α处理A549细胞后,磷酸化的GSK-3β和Akt蛋白在2 h后表达增加,4 h后无磷酸化β-catenin蛋白表达也开始上调。结论：香烟烟雾诱导肺肿瘤组织中巨噬细胞释放炎性反应因子TNF-α,进而通过Akt/GSK-3β途径激活肿瘤细胞中Wnt/β-catenin信号通路。     

脂肪组织与恶液质 —— 白色棕色的敌友之争

人体的脂肪组织分为白色脂肪和棕色脂肪组织两种。白色脂肪主要负责储存能量,而棕色脂肪组织的主要作用 是产热和消耗能量。近期研究显示,在白色脂肪组织内还存在第三类脂肪组织即浅褐色脂肪组织,其由白色脂肪转化而来, 在功能上与棕色脂肪细胞相似,这一过程称为“白色脂肪棕色化”。白色脂肪棕色化是肿瘤恶液质脂肪代谢的重要特征之一。 一方面,其通过棕色化后热量消耗增加而影响代谢,引起脂肪减少;另一方面,棕色化本身也会参与肿瘤恶液质的发生、 发展全过程。肿瘤组织分泌的白介素 -6 和甲状旁腺激素相关蛋白两大驱动因子主要通过兴奋交感神经系统、去甲肾上腺素 释放,作用于脂肪细胞上的 β3 肾上腺素受体,再进一步激活相应转录因子和产热基因如UCP1 的表达,而引起棕色化。它 既是肿瘤恶液质发生的早期事件,又贯穿恶液质全程,可以通过早期发现、干预该过程的各个环节,改善临床结局,为肿 瘤恶液质的早期诊断、预防及治疗提供依据。     

AMPK活性对HeLa细胞内质网功能稳态的影响

目的:探讨腺苷酸活化蛋白激酶(AMPK)对HeLa细胞内质网应激的影响。方法:试验分为对照组(1‰ DMSO)、内质网应激诱导组(2 μg/mL衣霉素或500 nmol/L MG132内质网应激诱导剂诱导)和内质网应激干预组[衣霉素或MG132+2 mmol/L AMPK激动剂5-氨基咪唑-4-甲酰胺-1-B-呋喃核糖苷(AICAR)干预组、衣霉素或MG132+2 mmol/L AMPK激动剂二甲双胍干预组以及衣霉素或MG132+0.5 mmol/L AMPK抑制剂Compound C干预组],以探究各处理组中AMPK活性状态对内质网应激的影响。收集对数生长期的HeLa细胞,分组诱导孵育后,用Western blot检测HeLa细胞AMPK/T-172磷酸化水平及内质网应激标志蛋白(p-elf2α、Grp78和XBP-1s)的表达,并采用细胞内钙集群检测分析(Indo-1 ratiometric Ca²⁺ analysis)检测各组HeLa细胞内Ca²⁺浓度的变化。结果:衣霉素和MG132可诱导内质网应激标志蛋白p-elf2α、Grp78和XBP-1s的表达。AMPK激动剂AICAR和二甲双胍干预可降低上述3种内质网应激标志蛋白的表达,并降低细胞胞浆内因内质网应激导致的Ca²⁺浓度升高,与对照组比较,差异均有统计学意义(P均<0.05)。AMPK抑制剂Compound C的干预对上述内质网应激标志蛋白的表达无明显影响(P均>0.05)。结论:AMPK激活能缓解HeLa细胞中的内质网应激,维持细胞内质网的功能稳态,可能对提高肿瘤细胞的应激耐受能力起到主要作用。     

过表达STAT1与CD74CD44促进结肠癌细胞粘附和迁移的相关性

目的 探讨信号转导和转录激活子1(STAT1)与CD74/CD44在结肠癌中异常表达与肿瘤转移的相关性.方法 培养结肠癌细胞株Ls-174-T,待其生长至对数生长期,传至第3代收集肿瘤细胞,各细胞分为3份.1份行RT-PCR、Western blotting方法检测STAT1与CD74/CD44表达情况;1份检测定量粘附细胞数;1份以划痕实验检测细胞迁移能力.统计分析比较STAT1与CD74/CD44在结肠癌细胞中的异常表达情况及与肿瘤迁移和粘附能力的相关性.结果 RT-PCR、Western blotting结肠癌组织中STAT1与CD74/CD44的蛋白及mRNA表达显著高于正常结肠组织,两组相比具有统计学差异(P＜0.05).MTT法检测结果显示,不同作用时间(0、6、12、24、48 h)不同剂量STAT1与CD74/CD44过表达质粒(0.000、0.001、0.010、0.060、0.100 mg/ml)干预后,结肠癌细胞体外粘附能力明显加强,与对照组(0.000 mg/ml各组)相比,差异有统计学意义;Transwell结果显示,不同作用时间(0、6、12、24、48 h)不同剂量STAT1与CD74/CD44过表达质粒(0.000、0.001、0.010、0.060、0.100 mg/ml)干预后,结肠癌细胞体外迁移能力随着时间及剂量的增加而明显加强,与对照组(0.000mg/ml各组)相比,差异有统计学意义.结论 STAT1与CD74/CD44在结肠癌细胞中高表达,从而调节结肠癌细胞粘附和迁移能力的作用,表明STAT1与CD74/CD44在结肠癌发生进展中可能与肿瘤的侵袭和转移密切相关.     

干酪乳杆菌对二甲基苯蒽诱发大鼠乳腺肿瘤的抑制作用及其免疫学机制

目的：探讨干酪乳杆菌对二甲基苯蒽（DMBA）诱发的大鼠乳腺肿瘤的抑制效果和对免疫功能的影响。方法：雌性SD大鼠按体质量随机分为正常对照组、模型组、低剂量和高剂量干酪乳杆菌干预组。模型组及低、高剂量干酪乳杆菌干预组大鼠右侧臀部皮下一次性注射100 mg/kg DMBA建立乳腺癌模型。低和高剂量干酪乳杆菌干预组分别灌胃给予4和8 mL/（kg·d）干酪乳杆菌（1×10⁸ CFU/mL）,正常对照组和模型组均给予5 mL/（kg·d）大豆油灌胃。每天1次,持续16周后处死大鼠,完整剥离肿瘤组织及脏器,计算各组大鼠乳腺癌发生率、抑瘤率及脏器指数。流式细胞术检测大鼠外周血中自然杀伤细胞（NK）活性和T淋巴细胞亚群分布。酶联免疫吸附实验（ELISA）检测血清中细胞因子IL-4、IL-6、IL-10、IL-12、IFN-γ和TNF-α水平。结果：正常对照组大鼠无肿瘤发生,模型组、低剂量和高剂量干酪乳杆菌干预组均有肿瘤发生。与模型组比较,高剂量干酪乳杆菌组大鼠肿瘤潜伏期延长,肿瘤发生率和平均瘤质量降低（P均 < 0.05）;抑瘤率达到41.2%;且该组胸腺指数显著升高（P < 0.05）;TCRαβ⁺CD161a⁺NK细胞百分比、CD3⁺CD8⁺T细胞百分比均显著升高（P均 < 0.05）;血中CD3⁺Foxp3⁺细胞百分比明显下降（P < 0.05）。ELISA结果显示,与正常对照组比较,模型组血清中IL-4水平明显降低,而IL-6、IL-12和TNF-α水平显著升高（P均 < 0.05）;与模型组比较,高剂量干酪乳杆菌干预组,血清IL-4、IL-10浓度显著增高,IL-6、IL-12浓度显著降低（P均 < 0.05）;低和高剂量干酪乳杆菌干预组血清中TNF-α浓度均显著下降（P均 < 0.05）。结论：干酪乳杆菌对乳腺癌大鼠肿瘤生长具有一定抑制作用,其作用机制可能与干酪乳杆菌调节CD4⁺、CD8⁺T细胞、NK细胞及调节性T细胞等免疫细胞分布,改善炎性相关细胞因子水平,从而提高机体免疫调节作用有关。     

小鼠Lewis肺癌模型制备方法的比较研究

目的 探讨不同方法制备小鼠Lewis肺癌模型的可行性及相关技术的改良.方法 采用体外培养细胞法、胰酶消化法、胶原酶法和匀浆法制备的不同浓度的细胞悬液皮下注射C57BL/6小鼠,观察不同方法获得的细胞数、成瘤率、成瘤时间、肿瘤体积、离体肿瘤重量、荷瘤鼠的生活习性等,判定改良技术的可行性.结果 体外培养细胞法可以获得所需细胞,成瘤率100%.而胰酶消化法、匀浆法获得的细胞较少,而且成瘤率较低,约80%～90%和60%～75%.胶原酶法则是几种方法中获得细胞数最多的,成瘤率100%.结论 改良后的胶原酶法制备小鼠Lewis肺癌模型具有方法简便、成瘤率高、经济实惠的特点,为肿瘤的实验研究奠定了基础.     

Carcinogenicity Testing of the Cosmetic Dye: D&C Red No. 36

D&C Red No. 36, a drug and cosmetic dye commonly used for coloring lipsticks, was evaluated for its carcinogenicpotential in male and female Wistar rats. This dye has been shown to exhibit mutagenic activity towards Salmonellatyphimurium TA 98 in the presence of S9 mix. In the present study, 50 male and 50 female rats in each group weregiven diets containing D&C Red No. 36 at 2 different concentrations, 1,000 ppm and 2,000 ppm, for 78 weeks andsacrificed at week 98.It was found that dye treatment had no significant effect on the survival of either male or female animals as wellas the body weight gain in males. However, body weight gain of treated females was slightly lower than that of thecontrol group. Histopathological assessment demonstrated a number of benign and malignant tumors to havedeveloped in various organs of both dye treated and control groups. In male rats, benign liver tumors were found atincidences of 16.7% and 18.8% of the low (1,000 ppm) and high (2,000 ppm) dose groups, respectively, similar to the20% for the control group. Malignant tumors of the thyroid gland were observed only in the low dose and controlgroups, at 4.2% and 2%, respectively. In the high dose group, the incidences of lung, liver, urinary bladder and softtissue cancers were 4.2%, 2.1%, 2.1% and 2.1%, respectively, only one soft tissue cancer being observed in a controlgroup animal. In females, benign tumors were observed in the liver and mammary glands. The incidences of livertumors in the low and high dose groups were 12.8% and 16%, respectively, and 6% in the control group. Values formammary gland tumors were 10.6%, 10%, and 18% respectively. Malignant tumors were also observed in variousother organs, including the uterus, lung, kidney, thyroid, thymus and salivary gland, but the incidences were verylow (about 2-4%) and in dye treated male and female rats were not statistically different from those in the controlanimals.The results of the present study thus demonstrated that D&C Red No. 36 at the concentrations of 1,000 ppm and2,000 ppm in the diet is not carcinogenic either to male or female Wistar rats. While the occurrence of benign livertumors in female rats may be related to dye treatment, the lack of any apparent dose-dependence or any statisticallysignificant difference from the control group (P = 0.06) suggests that this is unlikely.     

Cetuximab potentiates oxaliplatin cytotoxic effect through a defect in NER and DNA replication initiation

Preclinical studies have demonstrated that the chemotherapeutic action of oxaliplatin, a third generation platinum derivative, is improved when combined with cetuximab, a monoclonal antibody inhibitor of epidermal growth factor receptors. To explore the mechanism of this synergistic benefit, we used HCT-8 and HCT-116, two human colon cancer cell lines, respectively, responsive and non-responsive to the oxaliplatin/cetuximab combination. We examined the effect of drug exposure on glutathione-S-transferase-mediated oxaliplatin detoxification, DNA-platinum adducts formation, cell cycle distribution, apoptosis, and the expression of multiple targets involved in DNA replication, recombination, and repair. The major changes we found in HCT-8 were a stimulation of oxaliplatin-DNA adduct formation associated with reduced expression of the key enzyme (excision repair cross complementation group1: ERCC1) in the key repair process of oxaliplatin-DNA platinum adduct, the nucleotide excision repair (NER), both at the mRNA and protein levels. We also observed a reduced expression of factors involved in DNA replication initiation, which correlates with an enrichment of cells in the G1 phase of the cell cycle as well as an acceleration of apoptosis. None of these changes occurred in the non-responsive HCT-116 cell that we used as a negative control. These findings support the fact that cetuximab potentiates the oxaliplatin-mediated cytotoxic effect as the result of inhibition of NER and also DNA replication initiation.     

Curtailing side effects in chemotherapy: a tale of PKCδ in cisplatin treatment

The efficacy of chemotherapy is often limited by side effects in normal tissues. This is exemplified by cisplatin, a widely used anti-cancer drug that may induce serious toxicity in normal tissues and organs including the kidneys. Decades of research have delineated multiple signaling pathways that lead to kidney cell injury and death during cisplatin treatment. However, the same signaling pathways may also be activated in cancer cells and be responsible for the chemotherapeutic effects of cisplatin in tumors and, as a result, blockade of these pathways is expected to reduce the side effects as well as the anti-cancer efficacy. Thus, to effectively curtail the side effects, it is imperative to elucidate and target the cell killing mechanisms that are specific to normal (and not cancer) tissues. Our recent work identified protein kinase C δ (PKCδ) as a new and critical mediator of cisplatin-induced kidney cell injury and death. Importantly, inhibition of PKCδ enhanced the chemotherapeutic effects of cisplatin in several tumor models while alleviating the side effect in kidneys, opening a new avenue for normal tissue protection during chemotherapy.     

Vitamins A, C and E and the risk of breast cancer: results from a case-control study in Greece.

Although several dietary compounds are hypothesized to have anticarcinogenic properties, the role of specific micronutrients in the development of breast cancer remains unclear. To address this issue, we assessed intake of retinol, beta-carotene, vitamin C and vitamin E in relation to breast cancer risk in a case-control study in Greece. Eight hundred and twenty women with histologically confirmed breast cancer were compared with 1548 control women. Dietary data were collected through a 115-item semiquantitative food frequency questionnaire. Data were modelled by logistic regression, with adjustment for total energy intake and established breast cancer risk factors, as well as mutual adjustment among the micronutrients. Among post-menopausal women, there was no association between any of the micronutrients evaluated and risk of breast cancer. Among premenopausal women, beta-carotene, vitamin C and vitamin E were each inversely associated with breast cancer risk, but after mutual adjustment among the three nutrients only beta-carotene remained significant; the odds ratio (OR) for a one-quintile increase in beta-carotene intake was 0.84 (95% confidence interval 0.73-0.97). The inverse association observed with beta-carotene intake, however, is slightly weaker than the association previously observed with vegetable intake in these data, raising the possibility that the observed beta-carotene effect is accounted for by another component of vegetables.     

Liver cancer risk, coffee, and hepatitis C virus infection: a nested case-control study in Japan

We examined hepatocellular carcinoma mortality in relation to coffee consumption and anti-hepatitis C virus (HCV) antibody seropositivity in a nested case-control study involving 96 cases. The multivariate-adjusted odds ratios (95% confidence interval) for daily coffee drinkers vs non-drinkers were 0.49 (0.25-0.96), 0.31 (0.11-0.85), and 0.75 (0.29-1.92) in all cases, in HCV-positive and in HCV-negative individuals, respectively.     

血管内皮生长因子C和Podoplanin对老年直肠癌淋巴结转移预后评价的价值

目的 探讨血管内皮生长因子C（VEGF-C）、Podoplanin在老年直肠癌淋巴结转移组织中的表达及其与预后的关系。方法 免疫组织化学法研究VEGF-C、Podoplanin在老年直肠癌及其相应淋巴结转移癌组织中的表达,同时了解术后随访情况。结果 老年直肠癌淋巴结转移组织中VEGF-C、Podoplanin的表达率均高于其相应的原发癌组织。有淋巴结转移的老年直肠癌组织VEGF-C、Podoplanin的表达显著高于无淋巴结转移的癌组织,差异有统计学意义（P<0.05）。VEGF-C、Podoplanin的表达水平和淋巴结转移是影响老年直肠癌患者预后的重要因素。结论 VEGF-C及Podoplanin在老年直肠癌淋巴结转移组织中的高表达,与直肠癌的预后有关。两者联合可以作为判断老年直肠癌淋巴结转移患者预后的检测指标。     

小鼠红白血病细胞FBL-3的生物学特性

 目的　探讨小鼠红白血病细胞FBL-3的生物学特性。方法　观察小鼠红白血病FBL-3细胞光镜下的形态、生长曲线、体外克隆形成率及细胞免疫组织化学染色情况;流式细胞术分析细胞周期分布以及MHC分子的表达情况;常规细胞遗传学方法分析染色体核型,PCR检测性别基因Sry;MTT法分析化疗药物敏感性;经尾静脉接种后观察C57BL／6小鼠肝、脾、肺、肾的病理变化。结果　FBL-3细胞呈梭形或多角形贴壁生长;细胞群体倍增时间为24.12 h。14 d和21 d克隆形成率分别为（35.23±1.44）%和（60.27±5.56）%。糖原染色阳性、氯醋酸染色部分阳性,过氧化物酶、碱性磷酸酶、丁酸染色均阴性。细胞周期：G0／G1细胞占（50.9±2.5）%,S期细胞占（36.3±1.4）％、G2／M期细胞占（13.8±0.8）％。对化疗药物阿糖胞苷、长春地辛、顺铂、丝裂霉素、甲氨蝶呤的半数抑制浓度分别为（0.49±0.04）、（0.87±0.09）、（3.77±0.32）、（1.66±0.16）μmol／L和（2.77±0.24）nmol／L。FBL-3细胞染色体数目在34～41条之间,表达H-2b分子,Sry基因阳性。静脉接种小鼠100 %发病;接种的细胞数量与存活时间呈线性关系;白血病细胞可以浸润肝、肺、脾和肾。结论　FBL-3细胞具有白血病细胞的特性,体外易于培养,容易建立小鼠模型,可作为研究白血病的理想动物模型。     

A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China

We investigated whether concurrent infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) in China, a hyperepidemic area for these infections, was associated with a higher risk of causing hepatocellular carcinoma (HCC) than each infection alone in a meta-analysis in China, 32 case-control studies involving 3201 cases and 4005 controls, identified from a computer-based literature search from 1966 to 2004. The pooled odds ratio and 95% confidence interval (CI) for HBsAg positivity was 14.1 (95% CI: 10.6-18.8); for anti-HCV/HCV RNA positivity was 4.6 (95% CI: 3.6-5.9); for HBsAg positivity and anti-HCV/HCV RNA negativity were 15.6 (95% CI: 11.5-21.3); for HBsAg negativity and anti-HCV/HCV RNA positivity were 8.1 (95% CI: 5.0-13.0); and positivity for both HBsAg and anti-HCV/HCV RNA was 35.7 (95% CI: 26.2-48.5). We conclude that HBV and HCV infections are important independent risk factors for HCC in China, and that dual infection by HBV and HCV is associated with a higher risk of causing HCC than each infection alone, suggesting a synergism between HBV and HCV.